Vesicle trafficking is defined as the vesicular transport of materials between different subcellular compartments of eukaryotic cells. Vesicles bud from a donor membrane and fuse with a recipient one carrying internalized materials from one site to another. Several protein complexes involving integral proteins of the vesicle and target membranes, such as Sec proteins and Rab proteins, help regulate vesicular transport by directing the vesicles to and from the correct membrane surface.
SEC22, BET1, and BOS1 are yeast genes involved in endoplasmic reticulum (ER)-to-Golgi protein transport. These genes code for small integral membrane proteins, named Sec22p, Bet1p, and Bos1p, respectively, with molecular masses ranging from 16 to 28 kDa. The amino-termini and the central regions of the proteins are hydrophilic, and the carboxy termini contain a transmembrane anchor. Sec22p, Bet1p, and Bos1p have all been identified as integral components of ER-to-Golgi vesicles (Lian, J. P. and Derro-Novick, S. (1993) Cell 73: 735-745; Rexach, M. F. et al. (1994) J. Cell Biol. 126: 1133-1148). SEC22 and BOS1 are further shown to cooperate in activating vesicles for docking or fusion with the Golgi membrane (Lian, J. P. et al. (1994) Nature 372: 698-701). Large protein complexes containing Sed5p, Bet1p, Bos1p, Sed22p, Sly1p, and Sec17p as well as several previously unknown proteins have been immunoprecipitated from detergent extracts of yeast cells arrested at a late step in ER-to-Golgi protein transport (S.o slashed.gaard, M. et al. (1994) Cell 78: 937-948). This is consistent with the notion that vesicle targeting and fusion require protein complex formation involving integral proteins of the vesicle and target membranes.
Rat homologs of Sec22p and Bet1p, rsec22 and rbet1, respectively, have recently been identified (Hay, J. C. et al. (1996) J. Biol. Chem. 271: 5671-5679). Recombinant rsec22 and rbet1 proteins are integral membrane components of 28 and 18 kDa, respectively, and each shows a predicted transmembrane domain near the carboxyl terminus. The two proteins are found to be active at the opposite ends of the ER-Golgi transport process, rsec22 on the ER surface and rbet1 on the Golgi surface. This suggests that rsec22 and rbet1 are involved in the trafficking of vesicles in opposite directions of transport between the ER and Golgi. Hay et al. (supra) suggest that rbet1 may also interact with or function in retention in the intermediate compartment between ER and Golgi.
The discovery of a new human vesicle trafficking protein and the polynucleotides encoding it satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention and treatment of disorders associated with cell proliferation and inflammation.